Human Immunodeficiency Virus (HIV) is presumably the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). HIV establishes a persistent infection in different cell types; many of the cells express an antigen, the CD4 receptor, as a binding site at their surface. In such cells, the first step of cell infection is represented by viral attachment with binding of the external envelope glycoprotein of HIV to the CD4 surface antigen of the cell. This binding is followed by a series of events involving virus envelope and target cell membrane fusion and internalization, through which the cell is infected. HIV infected cells may then infect other cells, forming syncytia (giant polynuclear cells). Syncytia formation between HIV-1 infected cells and uninfected CD4.sup.+ cells (cells having the CD4 receptor) involves an interaction between the CD4 receptor and the HIV surface envelope glycoprotein. This process is blocked by soluble CD4, antiCD4 and anti-V3 antibodies.
Cell fusion processes responsible for cell-to-cell spread of the virus in vivo make plasma neutralizing antibodies obsolete and leads to virus escape from the immune system already damaged by lymphocyte depletion. B lymphocytes activated by HIV produce different antibody populations. Some antibodies do not interfere with gp120-CD4 interaction, but block membrane fusion, the process responsible for cell infection. These antibodies are principally directed against the envelope glycoprotein V3 loop.
Due to the very high variability of V3 loop in different HIV-1 isolates, anti-V3 antibodies generally only neutralize the isolate against which the antibodies were produced. Therefore neutralization is limited to that isolate and is called isolate specific. These antibodies are effective by cell fusion inhibition, without any activity on cell-virus binding.
Several attempts have been made to inhibit HIV infection by V3 loop-related peptides raising questions as to the efficacy of such peptides. For example, De Rossi et al. [Virology 184, 187-196 (1991)] found that some V3 peptides enhanced viral infectivity. Other synthetic peptides from the V3 loop, cyclic or non cyclic, were ineffective in the critical step of cell fusion. Thus, antagonist peptides have not been developed which are capable of blocking virus-cell fusion and cell-to-cell fusion independently of the virus isolate.
More recently, several studies have demonstrated a CD4 independent route of cell infection for both HIV-1 and HIV-2, suggesting the existence of at least one alternative viral receptor. One of these putative non-CD4 HIV receptors has been recently identified on CD4-brain-derived cells and colon epithelial cells. This receptor is a neutral glycolipid, called galactosyl ceramide (GalCer). HIV infection of CD4.sup.- /GalCer.sup.+ cells in the brain and in the intestine may account for some of the HIV-associated disorders in these organs. Moreover, the presence of GalCer on the apical side of some mucosal epithelial cells may facilitate the entry of the virus during sexual intercourse. No peptide derived from the V3 loop has yet shown ability to block the GalCer receptor.
In response to some of these problems, radially branched systems using lysine skeletons in polymers have been used by J. P. Tam [Proc. Natl. Acad. Sci. U.S.A., 85, 5409-5413 (1988)] to develop antigens without the use of carriers. Those antigens were designed to generate vaccines against a variety of diseases. Specifically, antigens for generating vaccines against HIV infection are described by Tam in PCT patent application ser. no. W093/03766 and essentially include the sequence IGPGR (SEQ ID NO: 1) (IUPAC convention single letter nomenclature for amino acids) and are of eleven amino acids in length to be effective in eliciting useful immune responses. Id. at page 13, lines 29-31. Such antigens are not, however, considered as potential direct therapeutic approaches to any disease, but are intended to provoke an immunogenic response in the body.